RAS and BRAF proteins are frequently mutated in colorectal cancer (CRC) and have been associated with therapy resistance in metastatic CRC patients. RAS isoforms are considered to act as redundant entities in physiological and pathological settings. However, there is compelling evidence that mutant variants of RAS and BRAF have different oncogenic potentials and therapeutic outcomes. In this review we describe similarities and differences between various RAS and BRAF oncogenes in CRC development, histology, and therapy resistance. In addition, we discuss the potential of patient-derived tumor organoids for personalized therapy, as well as CRC modeling using genome editing in preclinical model systems to study similarities and discrepancies between the effects of oncogenic MAPK pathway mutations on tumor growth and drug response.

RAS和BRAF蛋白在结直肠癌（CRC）中经常发生突变，并且与转移性CRC患者的治疗耐药性相关。RAS同工型被认为在生理和病理环境中充当冗余实体。然而，有力的证据表明RAS和BRAF的突变体具有不同的致癌潜力和治疗结果。在这篇综述中，我们描述了各种RAS和BRAF之间的异同癌基因在CRC的发展，组织学和治疗耐药性中的作用。此外，我们讨论了将患者源性肿瘤类器官用于个性化治疗的潜力，以及在临床前模型系统中使用基因组编辑研究CRC建模，以研究致癌MAPK途径突变对肿瘤生长和药物反应之间的相似性和差异。